The polymorphisms of protein-tyrosine phosphatase receptor-type delta gene and its association with pediatric asthma in the Taiwanese population

Abstract

We previously reported an association between genetic differences of pediatric asthma subtypes and a short tandem repeat (STR) marker, D9S286. It has been known that the protein-tyrosine phosphatase receptor-type delta (PTPRD) gene is located downstream of D9S286 and that the physical distance between them is about 0.25 Mb. We selected and conducted genotyping on 76 single-nucleotide polymorphisms (SNPs) that encircle the genomic region of PTPRD in Taiwanese children with or without asthma. A total of 996 subjects were divided into testing group (674 subjects) and validation group (322 subjects). The results were further validated with the third subject group (611 subjects) recruited from different geographical regions. After Bonferroni correction, 3 out of 80 SNPs were found to be strongly significant (Po0.05/76 ¼ 0.000658) in the allele frequency test. This association was confirmed by validation groups. The results indicate that polymorphisms of PTPRD are strongly associated with pediatric bronchial asthma in the Taiwanese population.

Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation ( PVT1 ) as a novel regulator of the asthmatic phenotype in human airway smooth muscle

“…Interestingly, the mRNA profile in ASMCs from patients with severe asthma appears to be important in increased calcium influx in the smooth muscle, 11 atopy, 12 and possible immunomodulation in patients with acute exacerbations of airway disease, including asthma 14 . Furthermore, when confirming our array results using RT-PCR, we described mRNAs with expression that has previously been shown to be increased in response to dexamethasone (NAV2) 18 to regulate cell viability, cell growth, cellular proliferation, and/or airway remodeling ( NFIB , NOVA1 , PTPRD , and PGM5 )19, 20, 21, 22 and those acting as potential tumor suppressors in patients with lung carcinoma ( PTPRD and NNAT ) 23, 24. Furthermore, we describe a large increase in CHI3L1 expression, which has not only been reported in a number of patients with inflammatory diseases and cancer but also has been implicated in asthmatic patients, with the discovery of an allele that doubles the risk 25 .…”

Analyses of shared genetic factors between asthma and obesity in children

“…The PTPRD protein is a member of the protein tyrosine phosphatase (PTP) family involved in a variety of cellular processes including cell growth, differentiation and oncogenic transformation 35 . PTPRD showed suggestive association to asthma in the most recent GWAS26 as well as in a previous asthma study 36. Association with BMI or obesity has to our knowledge not been reported previously, although other members of the PTP family, such as LAR/PTPRF, have been associated with BMI and insulin resistance 35, 37.…”

Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes

“…33,34 Intriguingly, a recent genome-wide association study has implicated PTPRD as a locus for RLS. 35 Moreover, genetic variants of PTPRD associate with bronchial asthma, 36 which is reported to occur at higher rates in children with ADHD, 37 and RLS patients have been shown to have increased use of asthma medications. 38 Studies of the PTPRD gene in mice show high expression in the hippocampus, the only brain region reported to be enlarged in ADHD, 39 along with involvement in spatial learning, long-term potentiation and axonal guidance of motor neurons.…”